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Insulin Resistance Affects Sustained Response to Hepatitis C Treatment

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Greater insulin resistance was association with poorer response to pegylated interferon plus ribavirin regardless of hepatitis C virus (HCV) genotype, according to a meta-analysis described in the August 2011 issue of Alimentary Pharmacology and Therapeutics.

Insulin resistance -- or reduced ability of cells to respond to insulin, a precursor to diabetes -- has been linked to liver fibrosis progression and reduced response to interferon-based therapy in people with chronic hepatitis C. Conversely, chronic HCV infection may promote insulin resistance. Some research suggests this relationship is strongest for HCV genotype 3, but findings have not been consistent.

To shed further light on these associations, M. Eslam from Hospital Universitario de Valme in Seville, Spain, and colleagues performed a meta-analysis to evaluate the impact of insulin resistance -- determined using the HOMA-IR (homeostasis model assessment of insulin resistance) method -- on sustained virological response (SVR) to pegylated interferon (Pegasys or PegIntron) plus ribavirin for treatment-naive adult chronic hepatitis C patients.

The researchers identified relevant studies by searching the Medline and EMBASE databases through December 2010, finding 17 published articles that addressed the influence of insulin resistance on sustained response 24 weeks after completion of therapy. They excluded studies of treatment-experienced patients, those treated with conventional (vs pegylated) interferon, those using other antivirals, liver transplant recipients, and people coinfected with HIV.

Results 

  • Normal insulin sensitivity was associated with a higher SVR rate compared to insulin resistance, with an odds ratio (OR) of 2.86, or nearly 3-fold better response.
  • In a separate analysis by genotype, focusing on studies that used a HOMA-IR cut-off of 2 to define insulin resistance, SVR was significantly higher among patients with HOMA-IR < 2 for all genotypes:
    • HCV genotype 1: OR 2.16;
    • HCV genotypes 2 and 3: OR 3.06;
    • HCV genotype 4: OR 6.65.
  • Studies that found no association between HOMA-IR and SVR generally included easy-to-treat populations.
  • Other studies not finding such an association analyzed variables strongly related to insulin resistance -- such as body mass index, steatosis (fatty liver), age, and fibrosis -- and reported differences in handling and interpretation of HOMA-IR.

Based on these findings, the study authors concluded, "Elevated HOMA-IR was associated with a lower cure rate of patients with hepatitis C treated with [pegylated interferon alfa]/ribavirin irrespective of genotype, and the more difficult-to-treat cohort, the better the HOMA-IR prediction."

"[T]hese data need to be further confirmed in different populations, using euglycemic hyperinsulinemic clamp [method] as gold-standard, and taking ethnicity and obesity into account when evaluating changes in HOMA-IR over time," they added. "Better handling and interpretation of HOMA are mandatory until the development of new tools for assessment of insulin resistance."

Investigator affiliations: Unit for the Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain; Department of Digestive Disease Information & Research and Department of Medicine, Kurume University School of Medicine, Kurume, Japan; Department of Internal Medicine, Minia University, Minia, Egypt.

8/23/11

Reference

M Eslam, R Aparcero, T Kawaguchi, et al. Meta-analysis: insulin resistance and sustained virological response in hepatitis C. Alimentary Pharmacology and Therapeutics 34(3): 297-305 (free full text). August 2011.